Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on January 16, 2016 has been entered.
Applicant’s amendment filed on January 16, 2026 is acknowledged and has been entered. Claims 5, 9, 17-19 have been canceled. Claims 1-3 and 14-16 are amended. Claims 1-4, 6-8, 10-16 and 20-21 are pending.
Claims 1-4, 6-8, 10-16 and 20-21 are discussed in this Office action.
All of the amendments and arguments have been thoroughly reviewed and considered but are not found persuasive for the reasons discussed below. Any rejection not reiterated in this action has been withdrawn as being obviated by the amendment of the claims. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
This action is made NON-FINAL.
New Grounds of Rejection as Necessitated by Amendment
Information Disclosure Statement
The information disclosure statement (IDS) submitted on February 10, 2025, April 28, 2025 and May 8, 2025 was filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-4, 6-8, 10-11 and 14-16 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Giudice et al. (US Patent 10,927,412; February 2021).
With regard to claim 1, Giudice teaches a method of diagnosing and treating one or more symptoms of endometriosis in a subject in need thereof comprising:
(a) obtaining endometrial stromal cells (Abstract, col. 1-2, where gene expression analysis of endometrial cells is described; col. 1, where the stromal cell component of endometriosis is described; col. 8, line 11-14, where the sample includes “endometrial cells (e.g. an endometrial biopsy)”, line 51 to col. 9, line 7, where the expression within endometrial cells is tied to diagnosis of endometriosis; see also col. 14, line 41-65, where the sample source is described in more detail and includes endometrial cells);
(b) subjecting or having subjected the endometrial stromal cells to processing to produce cDNA (col. 16, lines 1-47, where cDNA is part of the gene expression analysis of Giudice);
(c) subjecting or having subjected the cDNA to PCR to detect RNA gene expression of one or more genes comprising: GJA3, GJA5, GJA8, GJA9, GJB1, GJB2, GJB3, GJB5, GJB6, GJB7, and GJC2 or receiving the results of the RNA gene expression assay (Table 15, where GJB2 and GJB6 are included in particularly relevant genes for diagnosis; col. 2-4, where the expression analysis of genes in Tables 7-15 are described; col. 5, col. 14, for example, where the determination of expression level is described in more detail as including RT-PCR or Q-PCR); and
(d) obtaining a diagnosis or diagnosing the subject with endometriosis if expression of the one or more genes is reduced relative to expression of the one or more genes in endometrial stromal cells from a subject without endometriosis (Table 15, where GJB2 and GJB6 are included in particularly relevant genes for diagnosis; col. 2-4, where the expression analysis of genes in Tables 7-15 are described; col. 5, col. 14, for example, where the determination of expression level is described in more detail as including RT-PCR or Q-PCR); and
(e) administering a treatment for one or more symptoms of endometriosis to the subject diagnosed with endometriosis (Abstract; col. 11, lines 43-61, where treatments for endometriosis are described; col. 6, lines 27-41, where therapeutic treatment is described).
With regard to claim 2, Giudice teaches a method of diagnosing and treating one or more symptoms of endometriosis in a subject in need thereof comprising:
(a) obtaining endometrial epithelial cells (Abstract, col. 1-2, where gene expression analysis of endometrial cells is described; col. 1, where the stromal cell component of endometriosis is described; col. 8, line 11-14, where the sample includes “endometrial cells (e.g. an endometrial biopsy)”; see also col. 14, line 41-65, where the sample source is described in more detail and includes endometrial cells);
(b) subjecting or having subjected the endometrial epithelial cells to processing to produce cDNA (col. 16, lines 1-47, where cDNA is part of the gene expression analysis of Giudice);
(c) subjecting or having subjected the cDNA to PCR to detect RNA gene expression of one or more genes comprising (col. 5, col. 14, for example, where the determination of expression level is described in more detail as including RT-PCR or Q-PCR):
(i) GJA3, GJA5, GJA8, GJA9, GJBl, GJB2, GJB3, GJB5, GJB6, GJB7, and GJC2 or receiving the results of the RNA gene expression assay (Table 15, where GJB2 and GJB6 are included in particularly relevant genes for diagnosis; col. 2-4, where the expression analysis of genes in Tables 7-15 are described; col. 5, col. 14, for example, where the determination of expression level is described in more detail as including RT-PCR or Q-PCR); and
(d) obtaining a diagnosis or diagnosing the subject with endometriosis if expression of the one or more genes is elevated relative to expression of the one or more genes in endometrial epithelial cells from a subject without endometriosis (Table 15, where GJB2 and GJB6 are included in particularly relevant genes for diagnosis; col. 2-4, where the expression analysis of genes in Tables 7-15 are described; col. 5, col. 14, for example, where the determination of expression level is described in more detail as including RT-PCR or Q-PCR); and
(e) administering a treatment for one or more symptoms of endometriosis to the subject diagnosed with endometriosis (col. 11, lines 43-61, where treatments for endometriosis are described; col. 6, lines 27-41, where therapeutic treatment is described).
With regard to claim 3, Giudice teaches a method of diagnosing and treating one or more symptoms of endometriosis in a subject in need thereof comprising
(a) obtaining endometrial stromal and epithelial cells (Abstract, col. 1-2, where gene expression analysis of endometrial cells is described; col. 1, where the stromal cell component of endometriosis is described; col. 8, line 11-14, where the sample includes “endometrial cells (e.g. an endometrial biopsy)”; see also col. 14, line 41-65, where the sample source is described in more detail and includes endometrial cells);
(b) subjecting or having subjected the endometrial stromal and epithelial cells to processing to produce cDNA (col. 16, lines 1-47, where cDNA is part of the gene expression analysis of Giudice);
(c) subjecting or having subjected the cDNA to PCR to detect RNA gene expression of one or more genes GJA3, GJA5, GJAS, GJA9, GJB1, GJB2, GJB3, GJB5, GJB6, GJB7, and GJC2 or receiving the results of the RNA gene expression assay (Table 15, where GJB2 and GJB6 are included in particularly relevant genes for diagnosis; col. 2-4, where the expression analysis of genes in Tables 7-15 are described; col. 5, col. 14, for example, where the determination of expression level is described in more detail as including RT-PCR or Q-PCR); and
(d) obtaining a diagnosis or diagnosing the subject with endometriosis if expression of the one or more genes is reduced relative to expression of the one or more genes in endometrial stromal cells from a subject without endometriosis and if the one or more genes is elevated relative to expression of the one or more genes in endometrial epithelial cells from a subject without endometriosis (Table 15, where GJB2 and GJB6 are included in particularly relevant genes for diagnosis; col. 2-4, where the expression analysis of genes in Tables 7-15 are described; col. 5, col. 14, for example, where the determination of expression level is described in more detail as including RT-PCR or Q-PCR); and
(e) administering a treatment for one or more symptoms of endometriosis to the subject diagnosed with endometriosis (col. 11, lines 43-61, where treatments for endometriosis are described; col. 6, lines 27-41, where therapeutic treatment is described).
With regard to claim 4, Giudice teaches a method of claim 1, wherein the endometrial cells are obtained from menstrual blood or an endometrial biopsy (col. 8, line 11-14, where the sample includes “endometrial cells (e.g. an endometrial biopsy)”).
With regard to claim 6, Giudice teaches a method of claim 1, wherein the treatment for one or more symptoms of endometriosis comprises anti- inflammatory drugs, interfering RNA, hormonal therapy, er and surgical removal of the affected tissue (col. 11, lines 43-61, where treatments for endometriosis are described; col. 6, lines 27-41, where therapeutic treatment is described).
With regard to claim 7, Giudice teaches a method of claim 1 or 3, wherein diagnosing the subject with endometriosis further comprises staging the endometriosis (col. 24, line 35 to col. 25, line 5, where staging of endometriosis is described).
With regard to claim 8, Giudice teaches a method of claim 7, wherein the endometriosis stage is superficial endometriosis (col. 24, line 35 to col. 25, line 5, where staging of endometriosis is described).
With regard to claim 10, Giudice teaches a method of claim 1, wherein the subject has been previously diagnosed with endometriosis (col. 24, line 35 to col. 25, line 5, where staging of endometriosis is described).
With regard to claim 11, Giudice teaches a method of claim 10, wherein the endometriosis is superficial endometriosis (stage I/II) or deep infiltrating endometriosis (stage III/IV) (col. 24, line 35 to col. 25, line 5, where staging of endometriosis is described).
With regard to claim 14, Giudice teaches a method of claim 1, wherein the one or more genes whose expression is reduced relative to expression of the one or more genes in endometrial stromal cells from a subject without endometriosis GJA3, GJA5, GJA8, GJA9, GJB 1, GJB2, GJB3, GJB5, GJB6, GJB7, and GJC2 (Table 15, where GJB2 and GJB6 are included in particularly relevant genes for diagnosis; col. 2-4, where the expression analysis of genes in Tables 7-15 are described; col. 5, col. 14, for example, where the determination of expression level is described in more detail as including RT-PCR or Q-PCR).
With regard to claim 15, Giudice teaches a method of claim 2, wherein the one or more genes whose expression is elevated relative to expression of the one or more genes in endometrial epithelial cells from a subject without endometriosis is GJA3, GJA5, GJA8, GJA9, GJB1, GJB2, GJB3, GJB5, GJB6, GJB7, and GJC2 (Table 15, where GJB2 and GJB6 are included in particularly relevant genes for diagnosis; col. 2-4, where the expression analysis of genes in Tables 7-15 are described; col. 5, col. 14, for example, where the determination of expression level is described in more detail as including RT-PCR or Q-PCR).
With regard to claim 16, Giudice teaches a method of claim 1, wherein step (b) comprises subjecting or having subjected the endometrial stromal cells to single cell processing in microfluidic chambers to produce cDNA (Abstract, col. 1-2, where gene expression analysis of endometrial cells is described; col. 1, where the stromal cell component of endometriosis is described; col. 8, line 11-14, where the sample includes “endometrial cells (e.g. an endometrial biopsy)”, line 51 to col. 9, line 7, where the expression within endometrial cells is tied to diagnosis of endometriosis; see also col. 14, line 41-65, where the sample source is described in more detail and includes endometrial cells).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 12-13 and 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Giudice et al. (US Patent 10,927,412; February 2021) as applied over claims 1-4, 6-8, 10-11 and 14-16 above and further in view of Kato et al. (Human Reproduction, 2007, 22(5):1214-1223).
Regarding claim 12-13 and 20, while Giudice teaches a method of analysis, Giudice does not teach cell sorting, as claimed.
With regard to claim 12, Kato teaches a method of claim 1, wherein the endometrial stromal cells are isolated by sorting the cells using endometrial stromal cell markers CD 10, CD 146, and CD 13 (Abstract, where CD13, p 125 “magnetic cell sorting” heading, where CD9 and CD13 were used for sorting).
With regard to claim 13, Kato teaches a method of claim 2, wherein the endometrial epithelial cells are isolated by sorting the cells using endometrial epithelial cell markers EpCam, CD45, and CD9 (Abstract, where CD13, p 125 “magnetic cell sorting” heading, where CD9 and CD13 were used for sorting).
With regard to claim 20, Kato teaches (ii) enriching or expanding the endometrial stromal and/or epithelial cells (Abstract, legend to Figure 2, p 1218, col. 1, where cells are enriched).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have adjusted the teachings of Giudice to include the cell sorting as guided by Kato to arrive at the claimed invention with a reasonable expectation for success. Giudice teaches “useful for diagnosing the presence or absence of endometriosis and the severity of endometriosis in a subject. The methods and compositions are also useful for distinguishing endometriosis from other uterine or pelvic pathologies in a subject” (Abstract). Kato teaches “Endometrial cells were obtained using enzymatic digestion from uterine hysterectomy for the treatment of uterine myoma and stained with Hoechst 33342 dye either alone or in combination with verapamil. The cells were then analysed using FACS. RESULTS: SP cells were present among normal human endometrial cells. Most SP cells were enriched in the CD92CD132 fraction. These SP cells showed long-term repopulating properties and produced gland (CD91)- and stroma (CD131)-like cells”. Therefore, one of ordinary skill in the art at the time the invention was made would have adjusted the teachings of Giudice to include the cell sorting as guided by Kato to arrive at the claimed invention with a reasonable expectation for success.
Claim(s) 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Giudice et al. (US Patent 10,927,412; February 2021) as applied over claims 1-4, 6-8, 10-11 and 14-16 above and further in view of Li et al. (Biotech Advances 2013, 31:312-317).
With regard to claim 21, Li teaches a method of claim 20, wherein the method further comprises subjecting or having subjected the enriched or expanded endometrial stromal and/or epithelial cells to single-cell processing in microfluidic chambers to produce cDNA (Fig 4, which describes a microfluidic system for single cell transcriptome analysis followed by single cell lysis and reverse transcription followed by flushing into further analysis by qPCR or microarrays).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have adjusted the teachings of Giudice to include the single cell microfluidic analysis of Li to arrive at the claimed invention with a reasonable expectation for success. Giudice teaches “useful for diagnosing the presence or absence of endometriosis and the severity of endometriosis in a subject. The methods and compositions are also useful for distinguishing endometriosis from other uterine or pelvic pathologies in a subject” (Abstract). Li teaches “potential therapeutic applications of MSC and discuss a systematic approach for molecular characterization of heterogeneous cell population using single-cell transcriptome analysis” (Abstract). Li also teaches “These microfluidic devices allow us to obtain reliable single-cell transcriptomes for investigating gene regulation. More recently, we developed phase-switch microfluidic devices with various designs to encapsulate individual cells into droplets for nanoliter RT reaction (Fig. 1). Using these microfluidic devices, we have successfully obtained whole genome transcriptomes with microarrays from individual cells (Fig. 2). The quality of single-cell data is similar to that from the population cell experiment in which 1 ng cDNA inputs was used” (p. 314, col. 1). Therefore, one of ordinary skill in the art at the time the invention was made would have adjusted the teachings of Giudice to include the single cell microfluidic analysis of Li to arrive at the claimed invention with a reasonable expectation for success.
Response to Arguments
Applicant’s arguments with respect to claim(s) 1-4, 6-8, 10-16 and 20-21 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Citation of Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Yu et al. (Molecular Human Reproduction, 2014, 20(3):260-270). Winterhager et al. (Human Reprod Update, 2015, 21(3):340-52). Schwab et al. (Human Reproduction, 2008, 23(4):934-943)
Conclusion
No claims are allowed. All claims stand rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEPHANIE KANE MUMMERT whose telephone number is (571)272-8503. The examiner can normally be reached M-F 9:00-5:30.
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/STEPHANIE K MUMMERT/Primary Examiner, Art Unit 1681
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